Exocrine pancreatic ductograms in insulin-dependent diabetes mellitus

OBJECTIVES: To examine the prevalence of abnormal pancreatic ductograms in patients with insulin-dependent diabetes mellitus (IDDM) and to determine the clinical characteristics of those patients. METHODS: Pancreatic exocrine morphology was studied by endoscopic retrograde pancreatography (ERP) in 43 patients with IDDM, 12 patients with islet cell antibody (ICA)-positive non-insulin-dependent diabetes mellitus (NIDDM), and 22 patients with ICA-negative NIDDM. RESULTS: ERP revealed a significantly higher prevalence of abnormal pancreatic ducts (dilation and stenosis, tortuosity, obstruction, and intraductal calculi) in the patients with IDDM (17/43, 40%) than in the patients with ICA-negative NIDDM (2/22, 9%, p = 0.018). IDDM patients who slowly progressed to insulin dependency more than 13 months after the onset of diabetes had a higher frequency of abnormal pancreatic ducts (13/22, 59%) than those who needed insulin therapy within 12 months after the onset (4/21, 19%, p = 0.016). There was no difference in duration of diabetes between the two groups. ICA-positive NIDDM patients also had a higher frequency of abnormal pancreatic ducts (7/12, 58%) than ICA-negative NIDDM patients (2/22, 9%, p = 0.0074). CONCLUSIONS: These results indicate that a high proportion of IDDM patients who have prolonged histories of non-insulin dependency with ICA suffer pancreatic exocrine impairment. A similarity between IDDM with a slowly progressive clinical course and fibrocalculous pancreatic diabetes seen in tropical countries also was suggested.     

Selective determination of non-enzymatic glycosylated serum albumin as a medium term index of diabetic control

Serum proteins are non-enzymatically glycosylated dependent on the concentration of free glucose and measurements of their concentration are used to control diabetic carbohydrate metabolism. Eight patients with insulin-dependent diabetes mellitus (IDDM) and 8 patients with non-insulin-dependent diabetes mellitus (NIDDM) with glycosylated hemoglobin levels of at least 10.5% were studied during a 6-week period of antidiabetic therapy. Glycosylated serum albumin (GSA) and glycosylated total serum proteins (GSP) were measured weekly using an affinity chromatography procedure. The fructosamine test (FA) and the measurement of mean blood glucose (MBG) were also carried out weekly. Glycosylated hemoglobin and its glucose adduct HbA1c were determined at 14-day intervals (HPLC-method). All measured parameters decreased during the period of the study. The correlation coefficients for the glycosylated proteins versus the MBG determined one week earlier were highest for GSA [IDDM: r(GSA/MBG-1) = 0.726, p < 0.001 for the single values and 0.984, p < 0.001 for the mean values; NIDDM: r (GSA/MBG-1) = 0.636, p < 0.001 for the single values and 0.986, p < 0.001 for the mean values]. The differences between the IDDM and NIDDM group probably occurred because 6 NIDDM patients were taking glibenclamide (7.0-10.5 mg/day) which is known to inhibit the glycosylation reaction of albumin. The fructosamine test is more prone to interferences than the selective determination of GSA. GSA determination therefore, gives precise data in medium term diabetic control.     

Increased intracellular calcium and altered phorbol dibutyrate binding to intact platelets in young subjects with insulin-dependent and non-insulin-dependent diabetes mellitus

Intracellular calcium ([Ca2+]i) and phorbol ester binding were studied in intact platelets of young patients with insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. Our objective was to evaluate disturbances in calcium regulation and signal transduction in platelets of diabetics. [Ca2+]i in platelets of the IDDM group (135 +/- 20 nmol/L) under basal conditions was significantly higher than that of the control group (81 +/- 8 nmol/L, P = .019), whereas at 60 seconds after stimulation with 0.1 National Institutes of Health (NIH) U/mL thrombin, [Ca2+]i in the NIDDM group (484 +/- 36 nmol/L) was significantly higher than that of the controls (347 +/- 22 nmol/L, P = .003) and IDDM group (360 +/- 45 nmol/L, P = .04), respectively. Phorbol 12,13-dibutyrate (PdBu) maximal binding capacity (Bmax) in the IDDM group was significantly lower than that in the control group either under basal conditions or after stimulation with thrombin (P = .0034 and P = .015, respectively). Bmax in the NIDDM group was significantly lower than that in the controls only after stimulation with thrombin (P = .047). The Kd for PdBu of the IDDM group was lower than that of the control group under basal conditions (P = .017). When analyzing the pooled data of all subjects, a significant correlation was observed between Bmax and Kd (under basal conditions, r = .544, P < .0001; after stimulation, r = .601, P < .0001). Our results support the idea that the increased affinity for PdBu may compensate for the decreased binding capacity. We interpret the data as indicating that the change in the binding of phorbol ester to protein kinase C (PKC) units may result in an altered PKC/calcium interaction in the pathogenesis of diabetes mellitus. Our study indicates that such metabolic derangements of [Ca2+]i have already been developing in young diabetic patients.     

Clozapine reduces rehospitalization among schizophrenia patients

Diabetes mellitus positive for antibodies to glutamate decarboxylase is heterogeneous as far as the degree of impairment of endogenous insulin release, though antibodies to glutamate decarboxylase are the most useful marker for future insulin deficiency. To investigate what determines the prognosis of diabetes mellitus positive for antibodies to glutamate decarboxylase, we measured HLA-DRB1 alleles in three groups: 77 cases of insulin-dependent diabetes mellitus (IDDM), 44 of non-insulin-dependent diabetes mellitus (NIDDM) with secondary failure of oral hypoglycemic therapy, and 22 of NIDDM well controlled by diet and/or sulfonylurea agents. The proportion of susceptible and resistant alleles to IDDM determined the degree of insulin deficiency, and comparison of IDDM to NIDDM well controlled by diet and/or sulfonylurea agents revealed significant differences in DRB1*0405 (P < 0.05; RR = 2.82 and RR = 0.89, respectively) and DRB1*1502 (P < 0.001; RR = 0.02 and RR = 2.19, respectively). This study revealed that HLA-DRB1 alleles contribute to determining the prognosis of Japanese diabetes mellitus positive for antibodies to glutamate decarboxylase.     

Factors related to glycemic control in IDDM and insulin-treated NIDDM patients in current practice. A comparison of care policies. SIEMTIC Group. Studio Italiano Epidemiologico Multicentrico su Terapia Insulin e Controllo Metabolico

OBJECTIVE: To evaluate, under routine conditions, the relation between different diabetes care policies and glycemic control through a by-center analysis procedure aimed at reducing some drawbacks of cross-sectional data. RESEARCH DESIGN AND METHODS: A survey on insulin-treated diabetes care management (IDDM and NIDDM) involved 16 Italian randomly selected diabetes outpatient clinics. A total of 2,142 representative patients were investigated. The standardized HbA1c average value of each center was related, by regression models, to some indicators of center care policy (average number of injections, average BMI, proportion of cases with recent fundus oculi examinations, or frequent visits) as well as to patients' average social levels (employment type). Homogeneity in patient admission criteria is assumed among the investigated centers as a basic condition for the procedure validity. Some known imbalance were controlled for both design and analysis. RESULTS: HbA1c showed a univariate inverse relation with daily number of injections in IDDM (P = 0.0009, r2 = 0.56) but not in NIDDM (P = 0.33). It was inversely related to both fundus examination (IDDM P = 0.04; NIDDM P = 0.099) and qualified employment (IDDM P = 0.06; NIDDM P = 0.026). A stepwise regression analysis left in the model insulin injections (P = 0.0002) in IDDM (total r2 = 0.68) and qualified employment (P = 0.016) and fundus examination (P = 0.14) in NIDDM (total r2 = 0.53), after controlling for age, sex, disease duration, insulin therapy starting delay, and insulin dose per kilogram. CONCLUSIONS: These results suggest that the confirmed benefits of a multiple-injection regimen in IDDM cannot be simply extrapolated to NIDDM, where patients' awareness and medical attention to complications proved to be the most important factors in current practice.     

Reduced Na(+)-K(+)-ATPase activity and plasma lysophosphatidylcholine concentrations in diabetic patients

A fraction from normal human plasma inhibiting Na(+)-K(+)-ATPase has been recently identified as lysophosphatidylcholine (LPC). The aim of this study was to investigate the existence of a relationship between the activity of the cellular membrane Na(+)-K(+)-ATPase and plasma LPC in human diabetes. We studied 10 patients with insulin-dependent-diabetes mellitus (IDDM), 14 patients with non-insulin-dependent diabetes mellitus (NIDDM), and 10 sex- and age-matched control subjects. Plasma LPC concentrations were increased in both IDDM and NIDDM patients compared with control subjects. Na(+)-K(+)-ATPase activity was reduced in both groups of patients in erythrocyte and platelet membranes. There was a significant correlation between the concentrations of plasma LPC and Na(+)-K(+)-ATPase activity in both erythrocyte and platelet membranes (P < 0.01). To investigate the effect of LPC on the enzyme, Na(+)-K(+)-ATPase activity was determined in erythrocyte membranes obtained from six healthy subjects after in vitro incubation with increasing concentrations of LPC (1-10 microM). Enzymatic activity was significantly reduced by in vitro LPC at a concentration of 2.5 microM, with a further decrease at 5 microM. These data suggest that the decrease in Na(+)-K(+)-ATPase activity in diabetes might be due to increased LPC concentrations.     

Diminished insulin clearance during late pregnancy in patients with type I diabetes mellitus

OBJECTIVE: Published data on bone metabolism in diabetes mellitus are conflicting. We have measured pyridinium crosslinks, biochemical markers of bone resorption, in order to evaluate bone resorption in diabetes mellitus. We also wished to investigate whether, as a consequence of chronic hyperglycaemia, pyridinoline is glycosylated to a greater extent in patients with diabetes mellitus. DESIGN AND PATIENTS: This cross sectional study included 142 patients (64 males, 78 females) with insulin dependent and non-insulin dependent diabetes mellitus (IDDM and NIDDM). These patients were compared to a healthy control group of 99 individuals (39 males and 60 females). MEASUREMENTS: Pyridinium crosslinks, glycosylated, free and total pyridinoline (gPYD, fPYD, tPYD) and free and total deoxypridinoline (fDPD, tDPD) were measured in a spot urine sample by high performance liquid chromatography (HPLC). Urinary creatinine, albumin and glucose were also measured. RESULTS: In the diabetic group, values of urinary gPYD and tDYD were significantly lower than in controls. gPYD excretion was lowest in patients with severe glycosuria. Free pyridinium crosslinks, both fPYD and fDPD, were excreted to a significantly lower extent. The molar ratio of tPYD to tDPD was significantly increased in diabetes mellitus. CONCLUSIONS: Decreased excretion of tDPD suggests low bone resorption in IDDM and NIDDM. Pyridinoline is not glycosylated to a greater extent in diabetes mellitus and tends to be decreased in proportion to the degree of glycosuria. Excretion of gPYD, fPYD and fDPD is depressed in severe glycosuria. Diminshed degradation to the final products, fPYD and fDPD, might represent increased resistance to enzymatic activity or diminished enzymatic activity. The increased molar ratio tPYD/tDPD in urine suggests an increased ratio in bone collagen in diabetes mellitus.     

Outcome of trigger finger treatment in diabetes

Trigger finger is an underdiagnosed hand disorder causing disability in longstanding diabetic patients. Sixty diabetic patients [39 insulin-dependent diabetes mellitus (IDDM) and 21 non-insulin-dependent diabetes mellitus (NIDDM)] and 60 nondiabetic patients were examined. All were initially treated by steroid injections: failure to alleviate symptoms was the indication for surgery. The incidence of multiple digit involvement was higher in IDDM patients as compared with the control group (p < 0.001). The diffuse type was 1.45 times more frequent in IDDM and NIDDM than in nondiabetic patients (p < 0.008). The diabetic patients had a relatively longer duration of symptoms (p < 0.003). Significantly, a higher recovery rate upon steroid injection was achieved in control patients as compared with the diabetic ones (p < 0.001). IDDM patients required more surgery compared with NIDDMs and, in 13.3% of diabetic patients, the surgical outcome was not successful. Diabetic patients should be diagnosed early for multiple and diffuse types of trigger digits. Steroid injection as the first mode of therapy is highly recommended although not always successful. Surgery is the definitive treatment but requires a long course of physiotherapy and may be associated with some complications.     

The pancreas in diabetes mellitus. The echographic aspects

Forty patients with diabetes mellitus (25 with insulin-dependent and 15 with non-insulin dependent diabetes) were studied by means of US in order to evaluate possible volumetric alterations in the pancreas and their eventual progression over time. Thirty healthy subjects were also studied as a control group. The following variables were recorded: thickness of the head, body and tail of the pancreas and area of its head. The patients were also divided into 5 groups according to the age of diabetes (< 1, > 1, > 7, > 14, > 21 years). The results showed 25 IDDM patients to exhibit significant reduction in these variables relative to controls (p < = 0.01), especially in the body (average reduction -40%) and tail (average reduction -20%) of the pancreas. NIDDM patients exhibited non-significant reductions in pancreatic size. The study of the 5 groups of IDDM patients, divided according to the duration of diabetes, revealed all pancreatic variables to reduce more than in controls within a year since diagnosis, to exhibit relative increase during the next 7 years and finally to reduce again in the following years. These results show that anatomic damage to the pancreas occurs within the first year of diabetes. Moreover, IDDM was seen to alter the normal proportions among the single anatomic structures forming the pancreas, especially relative to two anatomic ratios--i.e., head/body and tail/body pancreatic thickness. The relative values in IDDM patients were markedly higher than those in controls (p < 0.001). The patients were again divided into 5 groups according to the age of diabetes: the values of the above ratios in the course of diabetes greatly differed from those observed in controls--i.e., they increased within the first year of diabetes, were steady during the next 7 years, and returned to normal values after 21 years of diabetes, which meant the return to the normal anatomic ratios among the three parts of the pancreas.     

Is PstI polymorphism of the angiotensin I converting enzyme gene associated with nephropathy development in non-insulin-dependent diabetes mellitus (preliminary study)

Nephropathy is a frequent complication of long term diabetes. Diabetic nephropathy is the major determinant of premature morbidity and mortality both in insulin-dependent (IDDM) and in non-insulin dependent-diabetes mellitus (NIDDM). There is good evidence that genetic predisposition plays a major role in development of diabetic nephropathy. This hypothesis is based on the observation that diabetic nephropathy clusters within families, both in IDDM and NIDDM. Components of the renin-angiotensin system (RAS) are plausible candidate genes to examine for a association with microalbuminuria and diabetic nephropathy. In this study we compared the distribution of PstI melting polymorphism at the ACE locus among NIDDM patients with diabetic nephropathy and in patients who, despite long duration of NIDDM, remain without this complication. The 220 NIDDM patients for whom DNA was available were classified into two groups according to their renal status: normoalbuminuric control subjects (n = 80) who are NIDDM patients with an A/C ratio < 2.5 and nephropathy cases (n = 140) who are NIDDM patients with A/C ratio > 2.5. Albumin excretion rate was assayed by radioimmunoassay. HbA1c was assayed using HPLC methods, creatinine--using Jaffe methods and DNA analysis using PCR reaction, and then after the amplification product was digested with PstI enzyme. The study revealed that PstI sequence differences ("+/= and -") in the ACE gene do not contribute to genetic susceptibility to diabetic nephropathy in NIDDM.     

Characterization of cellular defects of insulin action in type 2 (non-insulin-dependent) diabetes mellitus

Seven non-insulin-dependent diabetes mellitus (NIDDM) patients participated in three clamp studies performed with [3-3H]- and [U-14C]glucose and indirect calorimetry: study I, euglycemic (5.2 +/- 0.1 mM) insulin (269 +/- 39 pM) clamp; study II, hyperglycemic (14.9 +/- 1.2 mM) insulin (259 +/- 19 pM) clamp; study III, euglycemic (5.5 +/- 0.3 mM) hyperinsulinemic (1650 +/- 529 pM) clamp. Seven control subjects received a euglycemic (5.1 +/- 0.2 mM) insulin (258 +/- 24 pM) clamp. Glycolysis and glucose oxidation were quantitated from the rate of appearance of 3H2O and 14CO2; glycogen synthesis was calculated as the difference between body glucose disposal and glycolysis. In study I, glucose uptake was decreased by 54% in NIDDM vs. controls. Glycolysis, glycogen synthesis, and glucose oxidation were reduced in NIDDM patients (P < 0.05-0.001). Nonoxidative glycolysis and lipid oxidation were higher. In studies II and III, glucose uptake in NIDDM was equal to controls (40.7 +/- 2.1 and 40.7 +/- 1.7 mumol/min.kg fat-free mass, respectively). In study II, glycolysis, but not glucose oxidation, was normal (P < 0.01 vs. controls). Nonoxidative glycolysis remained higher (P < 0.05). Glycogen deposition increased (P < 0.05 vs. study I), and lipid oxidation remained higher (P < 0.01). In study III, hyperinsulinemia normalized glycogen formation, glycolysis, and lipid oxidation but did not normalize the elevated nonoxidative glycolysis or the decreased glucose oxidation. Lipid oxidation and glycolysis (r = -0.65; P < 0.01), and glucose oxidation (r = -0.75; P < 0.01) were inversely correlated. In conclusion, in NIDDM: (a) insulin resistance involves glycolysis, glycogen synthesis, and glucose oxidation; (b) hyperglycemia and hyperinsulinemia can normalize total body glucose uptake; (c) marked hyperinsulinemia normalizes glycogen synthesis and total flux through glycolysis, but does not restore a normal distribution between oxidation and nonoxidative glycolysis; (d) hyperglycemia cannot overcome the defects in glucose oxidation and nonoxidative glycolysis; (e) lipid oxidation is elevated and is suppressed only with hyperinsulinemia.     

Mannose, mannitol, fructose and 1,5-anhydroglucitol concentrations measured by gas chromatography/mass spectrometry in blood plasma of diabetic patients

Gas chromatography/mass fragmentography was applied to measure sugars in the plasma of patients with diabetes mellitus (DM). The isotope-dilution technique was used in the calculation of 1,5-anhydro-D-glucitol (1,5-AG), whereas reductive deuterization of the samples and regression analysis of the reduction products were used to calculate the concentrations of mannose, fructose and mannitol. The concentrations of mannose and glucose were closely and positively correlated both in insulin-dependent (IDDM; r = 0.74, P = 0.001) and non-insulin-dependent (NIDDM; r = 0.89, P = 0.001) DM. The close correlation was also encountered in serial samples taken from patients with widely fluctuating plasma glucose concentrations. The mannose/glucose ratio was increased in NIDDM (P = 0.007). The concentration of 1,5-AG was decreased in both types of DM, but more markedly in IDDM. The concentration was negatively correlated with glucose concentration (r = 0.071, P = 0.02) and HbAtc (r = 0.84, P = 0.001) in NIDDM. It was postulated that both mannose and glucose, by competing with 1,5-AG of renal tubular sugar carrier sites, contribute to the high urinary excretion of 1,5-anhydroglucitol leading to depletion of the sugar in the diabetic organism. The high concentrations of circulating mannose suggested further that the contribution of mannose to the adverse effects of hyperglycaemia should be examined. The study demonstrated that parallel use of the isotope-dilution and reductive deuterization techniques is quite useful in the analysis of monosaccharides in biological fluids.     

Platelet cNOS activity is reduced in patients with IDDM and NIDDM

Several studies in vitro and in vivo suggest that the nitric oxide (NO) production is impaired in diabetes mellitus. Reduced levels of NO could contribute to vascular alteration facilitating platelet-vascular wall interaction, adhesion of monocytes to endothelium, vascular smooth muscle proliferation and by decreasing endothelium-dependent vasodilation. In this study we evaluated the activity of the constitutive nitric oxide synthase (cNOS) in platelets of patients with insulin-dependent diabetes mellitus (IDDM) and with non-insulin-dependent diabetes mellitus (NIDDM). When compared to that of normal subjects, cNOS activity is significantly lower in patients with IDDM and with NIDDM (1.57 +/- 0.25 vs. 0.66 +/- 0.10 fmol/min/10(9) PLTs and 1.57 +/- 0.25 vs. 0.67 +/- 0.08, respectively; p<0.005). These data demonstrate that the platelet cNOS activity is decreased in diabetes mellitus.     

Myocardial infarct and diabetes mellitus: incidence, management and prognosis

The authors analyse the data of the Myocardial and Diabetes Register, where 2436 diabetic patients (pts) and 1448 pts with acute myocardial infarction (AMI) were registered between 1st of January, 1992 and 31st of December 1994. In the history of diabetic patients previous AMI was present in 14.4% of the cases. The 21.6% of the AMI pts had diabetes mellitus as well. According to the type of diabetes (IDDM and NIDDM) the prevalence of AMI in the history of the registered persons was significantly different: among pts with NIDDM the previous AMI was found 14.8% of the pts and only 2% of pts with IDDM (p = 0.012). The clinical picture of AMI was also different of AMI pts with and without diabetes: chest pain suggesting AMI was present 10.9% of pts with proved AMI and diabetes mellitus, and 86.2% of pts with AMI without diabetes (p < 0.0001). The Streptokinase treatment was more common among AMI pts without diabetes (18.2% versus 12.5% p = 0.022). The hospital lethality was significantly higher among AMI pts with diabetes (42.8% versus 29.4% (p < 0.0001). The poorer prognosis was independent of age.     

Plasma homocysteine is related to albumin excretion rate in patients with diabetes mellitus: a new link between diabetic nephropathy and cardiovascular disease?

The high risk of cardiovascular disease in patients with diabetes mellitus, particularly in those with nephropathy, is not completely explained by classical risk factors. A high plasma homocysteine concentration is an independent risk factor for cardiovascular disease but information on its association with diabetes is limited. Fasting homocysteine concentrations were measured in the plasma of 165 diabetic patients (75 with insulin-dependent [IDDM]; 90 with non-insulin-dependent diabetes [NIDDM]) and 56 non-diabetic control subjects. Other measurements included the prevalence of diabetic complications, glycaemic control, lipid and lipoprotein levels, vitamin status and renal function tests. Patients with NIDDM had higher homocysteine levels than control subjects, whereas IDDM patients did not (9.2 +/- 4.5 vs 7.7 +/- 2 micromol/l, p < 0.01; and 7.0 +/- 3 vs 7.4 +/- 2 micromol/l, NS). Univariate correlations and multiple regression analysis showed albumin excretion rate to be the parameter with the strongest independent association with homocysteine. Patients with both types of diabetes and nephropathy had higher plasma homocysteine concentrations than those without nephropathy. Increases of homocysteine in plasma were related to increases in the severity of the nephropathy. Fasting hyperhomocysteinaemia was considered as the mean of the plasma homocysteine for all control subjects (7.5 +/- 2.1 micromol/l) + 2 SD (cut-off = 11.7 micromol/l). Nephropathy was present in 80 % of diabetic patients with fasting hyperhomocysteinaemia. In conclusion, increases in fasting homocysteine in diabetic patients are associated with increased albumin excretion rate, especially in those with NIDDM, thus providing a potential new link between microalbuminuria, diabetic nephropathy and cardiovascular disease.     

Clinical characteristics and outcome of hyperglycaemic emergencies in Johannesburg Africans

In this prospective analysis we investigated the clinical characteristics of black South African diabetic patients admitted to hospital with hyperglycaemic emergencies. The study cases were selected from the medical admissions to an urbanized, Johannesburg academic hospital over a period of 12 months. Only patients with severe diabetic ketoacidosis (DKA) or hyperosmolar non-ketotic hyperglycaemia (HNKH) as defined in the text were included. Over the study period, we identified 58 patients with severe DKA (M: 32, F: 26) and 24 with HNKH (M: 14, F:10). Thirty-two of the patients with DKA (55.2%) were classified as having non-insulin dependent (Type 2) diabetes mellitus (NIDDM). Compared to the 26 subjects with insulin-dependent (Type 1) diabetes mellitus (IDDM), the NIDDM patients were older (51.7 vs 27.7 years) and had a significantly higher body mass index (BMI) (29.4 vs 23.5 kg m(-2), p = 0.002), and glucose levels 47.5 vs 34 mmol l(-1) p = 0.004). Mortality from DKA was 6.8 % and from HNKH 16.6%. Infection was the leading precipitating factor for both DKA and HNKH, followed by first presentation and noncompliance. We conclude that the majority of urban African patients admitted to hospital with DKA have NIDDM. Mortality from DKA among the black Africans in Johannesburg is low and comparable to the mortality in western Europe.     

Angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism, and diabetic retinopathy in subjects with IDDM and NIDDM

Angiotensin 1 converting enzyme (ACE) catalyses the step which generates angiotensin II, and also inactivates bradykinin, peptides which play a key role in modulating vascular tone. Plasma ACE levels are under genetic control and up to 50% of the variation is due to an insertion/deletion (I/D) polymorphism of ACE gene with highest levels found in DD homozygotes. Studies have shown an association of diabetic nephropathy and ischaemic heart disease with angiotensin converting enzyme gene polymorphism in subjects with diabetes. We examined the association between diabetic retinopathy and ACE gene insertion/deletion polymorphism in 363 subjects with NIDDM (aged 68.3 +/- 10.7 years; 201 male, 162 female), 186 subjects with IDDM (aged 42.4 +/- 15.0 years; 100 male, 86 female) and 98 controls. These subjects were characterized for ACE I/D polymorphism employing standard primers. Diabetic retinopathy was diagnosed by ophthalmoscopy through dilated pupils by an ophthalmologist and classified as non-proliferative or proliferative retinopathy. As expected, diabetic retinopathy was strongly associated with duration of diabetes (p < 0.001) in both IDDM and NIDDM. Any retinopathy was present in 51% subjects with IDDM and 49% of subjects with NIDDM, while 22% of IDDM subjects and 5% of subjects with NIDDM had proliferative retinopathy. The frequency of I allele was 0.477 vs 0.482 vs 0.510 and D allele was 0.523 vs 0.518 vs 0.490, among subjects with IDDM, NIDDM and controls, respectively. The frequency of ACE I/D genotype was similar in subjects with IDDM, NIDDM, and controls (chi 2 = 0.46, df = 4, p = ns). Presence or absence of retinopathy was not significantly associated with ACE genotype in subjects with IDDM (chi 2 = 3.42, df = 2, p = ns) or NIDDM (chi 2 = 0.51, df = 2, p = ns). Among subjects with retinopathy, there was no significant association between ACE genotype and type of retinopathy. Controlled for duration of diabetes, the frequency of I/D genotype was not significantly different in 271 subjects with retinopathy (IDDM and NIDDM combined) when compared with 86 subjects without retinopathy at 15 years or more after diagnosis of diabetes (chi 2 = 1.29, df = 2, p = ns). These findings indicate that I/D polymorphism of ACE gene is not a useful marker and is unlikely to play a major role in determining genetic susceptibility to diabetic retinopathy or the severity of diabetic retinopathy.     

Apolipoprotein(a) concentrations in type 2 (non-insulin dependent) diabetic patients from Romania

Several studies suggested that lipoprotein (a)-Lp(a) is an independent atherogenic risk factor. Since non-insulin-dependent diabetes mellitus (NIDDM) is characterized by an increased risk of coronary heart disease (CHD) as related to the general population, the main purpose of our study was to compare the plasma levels of apolipoprotein (a)-(apo) (a) in 30 NIDDM patients hospitalized in our department, and in 20 non-diabetic controls from Timi?oara. Apo (a) values were similar in the two groups (medians, 95% confidence intervals 57 (50-107) in NIDDM versus 58 (51-106) U/l in controls; p = 0.9097). We found weak correlations between apo (a) and hemoglobin A1 (HbA1) (r = 0.42). A significant association was noticed between apo (a) and apo B, both in NIDDM (r = 0.71) and in control subjects (r = 0.81) p < < 0.001. The diabetic patients were screened for microalbuminaria with the MICRAL-test and we compared apo (a) levels in those having albumin excretion values above and under the cut-off point (20 mg/l). Apo (a) concentrations were similar in both samples. We found no association between apo (a) and plasma lipid values. NIDDM patients on fair glycemic control have similar apo (a) concentrations to non-diabetic subjects and they do not seem to be influenced by diabetes duration, HbA1, microalbuminuria and plasma lipid values Apo (a) and apo B are significantly correlated, both in diabetic and non-diabetic subjects.     

Polymerase chain reaction-single-strand conformation polymorphism analysis for the VHL gene in chemically induced kidney tumors of rats using intron-derived primers

In patients with insulin-dependent diabetes mellitus (IDDM), albuminuria reflects widespread vascular dysfunction. Albuminuria has been associated to defects of heparan sulfate proteoglycan (HSPG) within the extracellular matrix. Our hypothesis is that loss of HSPG in vascular walls reduces the HSPG-bound lipoprotein-lipase activity (LPLA), thereby causing elevated levels of plasma triglyceride (TG) seen in IDDM patients with albuminuria. The aim of the present study was to evaluate whether LPLA in muscle capillaries could be related to TG in IDDM patients with and without albuminuria. This is a cross-sectional study including ten healthy control subjects (group C), nine patients with IDDM and urinary albumin excretion rate (AER) of 30 mg/24 h or less (group D0) and 20 patients with IDDM and AER greater than 30 mg/24 h (group DA). Muscle LPLA, plasma TG, total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and very-low-density lipoprotein cholesterol (VLDL) were measured. Between groups no difference in total cholesterol, TG, VLDL, and LDL was found. In patients with albuminuria, LPLA was reduced compared to controls, however, the difference between the groups was not statistically significant [median (range)] 35.9 mU/g (20.4-103) versus 44.6 mU/g (28.2-57.2) and 40.9 mU/g (21.7-53.5) in group DA, C, and D0, respectively, p = 0.76. AER was not correlated to LPLA. An overall negative correlation between TG and LPLA was found; r = -0.33, p = 0.04, supported by an overall significant positive correlation between LPLA and HDL; r = 0.32, p = 0.045. We conclude that, in insulin-dependent diabetes mellitus, skeletal muscle lipoprotein-lipase activity is associated with plasma triglyceride, while an association between lipoprotein-lipase activity and urinary albumin excretion is questionable.     

Colchicum autumnale agglutinin activates all murine T-lymphocytes but does not induce the proliferation of all activated cells

To determine whether cytokines could have a role in the development of insulin-dependent diabetes mellitus (IDDM), we measured serum levels of cytokines derived from T helper 1 (interleukin-2 and interferon-gamma), T helper 2 (interleukin-4 and interleukin-10) lymphocytes and macrophages (tumour necrosis factor-alpha, interleukin-1 alpha and interleukin-1 beta) in patients before and after the onset of IDDM. Recently diagnosed IDDM patients had significantly higher levels of interleukin-2, interferon-gamma, tumour necrosis factor-alpha and interleukin-1 alpha than patients with either long-standing IDDM, non-insulin-dependent diabetes (NIDDM), Graves' disease, or control subjects (p < 0.05 for all). Compared with control subjects, patients with long-standing IDDM and those with NIDDM had higher interleukin-2 and tumour necrosis factor-alpha levels (p < 0.01 for all). Interleukin-4 and interleukin-10 were detectable in sera of patients with Graves' disease only, while interleukin-1 beta was not detectable in the serum of any control or test subject. To investigate whether high cytokine levels precede the onset of IDDM, we studied 28 non-diabetic identical co-twins of patients with IDDM, followed-up prospectively for up to 6 years after the diagnosis of the index. Levels of tumour necrosis factor-alpha and interleukin-1 alpha were elevated above the normal range more frequently in the eight twins who developed diabetes than in those 20 who did not (p < 0.005). Analysis of T helper 1 and T helper 2 profiles of the twin groups did not reveal a clear difference between prediabetic twins and twins remaining non-diabetic. These results support the notion that T helper 1 lymphocytes may play a role in the development of IDDM. This is associated with release of macrophage-derived cytokines, which is also a feature of the prediabetic period. The lack of evidence of a dominant T helper 1 profile of cytokine release before diabetes onset suggests that additional events, activating this arm of the cellular immune response, are required in the immediate prediabetic period.